The Laboratory of Malaria Immunology and Vaccinology (LMIV), formerly The Malaria Vaccine Development Branch (MVDB), is an NIAID initiative working in close collaboration with DMID to respond to the global need for vaccines against malaria. The mission of the LMIV is to discover and develop malaria vaccines through fundamental and clinical research in immunobiology and vaccinology, including investigations of malaria pathogenesis in the context of host immune responses. In support of this mission, the LMIV will develop new assays and animal models to assess vaccine candidates. LMIV will maintain a flexible infrastructure to permit rapid development and evaluation of new malaria vaccine candidates. An asexual blood-stage vaccine will elicit immune responses capable of either destroying malaria parasites in the blood stream or inhibiting parasites from infecting red blood cells. In either case, the net effect is to reduce or prevent burden of parasites and hence decrease the incidence, severity, or the complications of disease. Such a vaccine would target blood-stage parasite proteins since these antigens are abundantly expressed by parasites during persistent infections. It would act to prime the immune system for subsequent infection in infants or it would boost already present, yet weak, natural immunity in young children. Furthermore, a vaccine composed of multiple antigens will increase the number of individuals responding to at least one component of the vaccine. The inclusion of multiple alleles of polymorphic proteins would also minimize immune pressure on parasite selection, thus decreasing the likelihood of parasite breakthrough. Several animal studies have been completed to evaluate the AMA1-C2 vaccine. The antisera were effective in GIA against all 3 alleles. The AMA1-C2 combination has been formulated with Alhydrogel+ CPG 10104, a TLR9 angonist, was immunogenic, yet not toxic to rabbits in a toxicology study in compliance with Good Laboratory Practice. However, further development in human trials has been deferred to a new antigen combination involving AMA1 and MSP1-42 alleles, formulated with Alhydrogel and CPG 7909, the adjuvant with more safety records in humans.